The long-term research objectives of this laboratory involve elucidating the roles of the glycoprotein complex ASGP-1/ASGP-2 (SMC) in mammary cancer, in other cancers and in normal tissues. Our short-term plan focuses on the transcriptional regulation of SMC expression in the mammary gland, uterus and mammary tumors. Abnormal expression of SMC/MUC4 has been reported in rat mammary adenocarcinoma and in human breast, pancreatic, lung and colon carcinomas; particularly in cells of highly invasive tumors obtained from patient body fluids. Our recent studies described novel post-transcriptional regulatory mechanisms for the expression of SMC in mammary gland, which has important implications for breast cancer and mammary development. Thus, the overall goal of our proposed studies is to understand the functions of SMC in normal epithelial development and tumor progression, focusing particularly on the mammary gland and uterus, and the mechanisms by which regulation of its expression contribute to those functions. The hypotheses being tested in this work are: 1) SMC contributes to tumor progression, 2) SMC is regulated by a combination of transcriptional and post-transcriptional mechanisms and 3) SMC contributes to epithelial development, specifically to mammary development. Specific Aims are to: I)investigate the mechanism required for lactogenic hormone induction of SMC/rMUC4 using an in vitro model system, the Rama 37 rat mammary epithelial stem cell line, 2) study the role of PEA3 transcription factor in SMC expression in 13762 ascites cell line and rat primary mammary epithelial cells, and 3) investigate the mechanism implicated in uterine rMUC4 expression through TGFbeta-signaling using rat primary uterine epithelial cells.